MINIR-II: Minimally Invasive Neurosurgical Intracranial Robot

描述(申请人提供)：这个R01项目建立在一个非常成功的R21项目的基础上，该项目涉及使用形状记忆合金(SMA)致动器的微创神经外科颅内机器人(mini R-I)的开发和可行性，以及在连续MRI下对该设备进行评估，以切除猪脑中植入的“转移瘤”。在我们实现了R21项目的具体目标的同时，我们也发现了新的挑战，这是这次R01应用的基础。脑瘤是最令人恐惧的癌症并发症之一，发生在20%-40%的成年癌症患者中。尽管在治疗方面取得了许多进展，但这些患者的预后很差，中位生存期为4-8个月。无论是原发(固有)恶性肿瘤，还是继发性(转移性)恶性肿瘤，脑参与癌症患者都是毁灭性的，因为它威胁到个体的个性和身份，而且总是所有并发症中最有可能的，直接和严重地影响生活质量。目前，大多数脑肿瘤的最佳治疗方法是一次手术切除，以便于辅助治疗，如放疗和化疗。不幸的是，许多患者不能接受脑肿瘤的一次手术切除，因为病变的位置不合适(通常是深部的或常规神经外科技术无法触及的)，以及患者的一般健康状况不佳。为了解决这个问题，基于我们R21试点项目的成功，以及从中吸取的经验教训，我们建议开发一种完全与MRI兼容的mini R-II，并通过对临床相关的体外和体内猪以及人体身体模型的全面评估来证明mini R-II的安全性和有效性。正如设想的那样，mini R-II将在医生的直接控制下，目标信息仅从实时核磁共振获得，该实时MRI使用嵌入在mini R-II中的传感器的主动目标方法。为了实现mini R-II，我们将致力于四个具体目标：1)设计一种与MRI完全兼容的多自由度(DOF)刚性塑料实体的mini R-II，具有电缆驱动的关节、布线和电子线路的中空内芯、冲洗和吸入能力以及肿瘤切除能力；2)开发和表征能够塑造具有微型特征的几何复杂机器人连杆的多件模具，以生产完全一次性/一次性使用的mini R-II原型；3)开发mini R-II的跟踪和导航系统，该系统将允许可视化近端和远端结构，以精确定位和切除肿瘤，4)小R-II在明胶模体和临床相关的脑转移瘤模型中的安全性和有效性，包括身体猪模型、活猪模型和人身体模型。我们在这个项目结束时的目标是让mini R-II(在连续核磁共振下操作)准备好进行临床试验。 与公共卫生相关：脑瘤是最令人恐惧的癌症并发症之一，发生在20%-40%的成年癌症患者中，中位生存期为4-8个月。虽然初次手术切除是首选的方法，但由于病变的位置不佳和一般健康状况不佳，大多数患者不能接受这种手术。因此，该项目的目标是在开发mini R-I的R21试点项目的基础上开发完全与MRI兼容的mini R-II，根据该项目，mini R-II将由一个坚硬的塑料机体制成，并集成用于肿瘤切除的硬件，并将在连续MRI下运行。

DESCRIPTION (provided by applicant): This R01 project builds on a highly successful R21 project which involved the development and feasibility of a Minimally Invasive Neurosurgical Intracranial Robot (MINIR-I) using shape memory alloy (SMA) actuators as well as the evaluation of the device under continuous MRI for resection of an implanted "metastatic tumor" in swine brain. While we achieved the specific aims of the R21 project, we also discovered new challenges, which are the basis for this R01 application. Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients. Despite numerous advances in treatment, the prognosis for these patients is poor, with a median survival of 4-8 months. Whether a primary (intrinsic) malignancy, or a secondary (metastatic) malignancy, involvement of the brain in a cancer patient is devastating, because it threatens the very personality and identity of the individual, and is invariably the most likely of all complications o directly and severely affect the quality of life. Currently, the optimal treatment for most brain tumors involves primary surgical resection to facilitate adjuvant therapies such as radiation and chemotherapy. Unfortunately, many patients cannot undergo primary surgical resection of their brain tumor due to unfavorable location of the lesion (usually deep or otherwise inaccessible to conventional neurosurgical techniques), and poor general health of the patient. To address this problem, based on the success of our R21 pilot project, and the lessons learned therein, we propose to develop a fully MRI- compatible MINIR-II and demonstrate the safety and efficacy of MINIR-II through comprehensive assessments on clinically relevant ex vivo and in vivo swine and followed by human cadaver models. As envisioned, MINIR-II will be under the direct control of the physician, with targeting information obtained exclusively from real-time MRI that uses active targeting methods with the sensors embedded within MINIR-II. To realize MINIR-II, we will address four specific aims: 1) Design a fully MRI compatible multiple degree-of-freedom (DOF) MINIR-II of rigid plastic body with cable driven joints, hollow inner core for routing cablin and electronics, irrigation and suction capability, and tumor removal capability, 2) Develop and characterize a multi-piece mold capable of molding geometrically complex robot links with miniature features to produce a completely disposable/single use MINIR-II prototype, 3) Develop a tracking and navigation system for MINIR-II that will allow visualization of proximal and distal structures for accurate targeting and resection of the tumor, and finally 4) the safety and efficacy of MINIR-II in gelatin phantoms and clinically relevant models of metastatic brain tumor including, a cadaveric pig model, a live pig model, and a human cadaver model. Our goal at the end of this project is to have MINIR-II (operated under continuous MRI) ready for clinical trials. PUBLIC HEALTH RELEVANCE: Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients with a median survival of 4-8 months. Though primary surgical resection is the preferred approach, most patients cannot undergo this procedure due to an unfavorable location of the lesion and poor general health. Hence, the goal of this project is to develop fully MRI compatible MINIR-II based on the advances in the R21 pilot project for the development of MINIR-I, whereby MINIR-II will be made of a rigid plastic body with integrated hardware for tumor removal and will be operated under continuous MRI.